My Case: Cushings?

Pharma / TRT Testosterone Replacement
1

-age: 31
-height: 5’4"
-waist: 5’4"
-weight: 430lbs
-describe body and facial hair: Very hairy all over.
-describe where you carry fat and how changed: Mostly around the abdomen. Do have a buffalo hump and moon-like face.
-health conditions, symptoms [history]: Actually haven’t really had many problems with cholesterol or blood pressure or diabetes despite my weight. Just always been very fat. Have had long-standing mood problems such as depression and anxiety however. Would also say I have chronic exhaustion. Also some memory issues.

-Rx and OTC drugs, any hair loss drugs or prostate drugs ever: Adderall, Namenda, Wellbutrin.
-lab results with ranges
t 60ng/dL
estriadol 42
tsh 2.440
fsh 6.8
prolactin 11.3
Sorry no ranges, got them over the phone
-describe diet [some create substantial damage with starvation diets]:

I certainly overeat, and mostly don’t eat very clean. I know a lot about what a healthy diet looks like, I just don’t have time/money/energy to cook and eat clean in the amounts my appetite demands. And when I try to deny the sheer amount I just feel even more like shit.
-describe training [some ruin there hormones by over training]:
Did Starting Strength a few years ago with a friend, and got to the point I was squatting 300, but with a wideish stance, and my knee started hurting and my friend went back to school, and I didn’t follow through from there. Pretty sedentary at the moment.
-testes ache, ever, with a fever? No
-how have morning wood and nocturnal erections changed: nonexistant

After long feeling unwell about myself, and wanting to better understand myself, and do whatever it takes to get to where I want to be, I finally found myself in the office of an endocrinologist a little over a month ago. I’ve been trying to educate myself about what has been found since then, and this forum has been of help. I’m posting here hoping to get advice, or maybe a sanity check.

So far we have found that I have hypogonadism and azoospermia. So far in response he is prescribing me HCG. I’ve brought up an AI and so far he is non-committal, but I plan to press more for one. I also am not clear why HCG and not HMG since I believe the cost would be the same with my insurance. No actual T replacement has been mentioned, I take it because it itself would have a neutral or negative effect to what is currently the primary goal of restoring fertility?

I also think that the amount of HCG may be much larger than would be optimal. Currently he is prescribing 2000IU EOD, which I haven’t started yet. Wednesday is the day I go in next to talk to him, and have a nurse show me how to inject. Isn’t that a lot? I also haven’t confirmed this, but I think he wants me to take it IM instead of SubQ. I seem to get the impression there is no good reason for this?

Also I will be bringing up Cushings to him. Mostly going off of Male Hypogonadism - Genitourinary Disorders - Merck Manuals Professional Edition which I came across wanting to learn about hypogonadism I found the suggestion to test for Cushing’s if their is clinical suspicion. I had never heard of it, but at the moment I feel, ehm, that clinical suspicion would be warranted. So I’m wanting to be tested for that. But I’m worried that I could be turning into too much of a hard case for this endo.

I did also have an accident as a child in which I fell off a swing set and landed on my testicles. I was happy presuming that was the cause of all of this, but I wouldn’t suspect that would itself explain the full list of Cushing’s symptoms.

Any advice or suggestions? Should I smile and nod at 2000IU HCG EOD and lower the dose to something more reasonable? Is there any reason to delay starting HCG until Cushing’s is confirmed or ruled out? Should I refuse to take gonadotropins without an AI? Should I insist on HMG instead of or as an adjunct to HCG? Is there something I’m missing?

Thanks in advance for your attention to my case.

2

Cortisol levels, CBC and differential, blood glucose before a meal, and urinalysis would be helpful.

3

[quote]C27 H40 O3 wrote:
Cortisol levels, CBC and differential, blood glucose before a meal, and urinalysis would be helpful.[/quote]

Of those at present I only have CBC and that without differential, and from most of a year ago. The rest I’ll have to aim for in the near future.

CBC without Diff
WBC 7.0 4.0-11.0 K/ul
RBC 5.13 4.20-5.80 M/uL
HGB 13.6 13.0-17.0 g/dL
HCT 41.3 39.0-52.0 %
MCV 80.5 80.0-94.0 fL
MCH 26.6 27.0-33.0 pg
MCHC 33.0 32.0-36.0 g/dL
RDW 16.8 11.5-15.5 %
PLT 202 150-400 K/uL

With note: not anemic, blood lines are normal

Edit: Actually, I think I do also have fasting glucose:
GLU 85 mg/dL (70-99)

4

I wouldn’t think cushings from what I see. Your appetite would most likely be suppressed with Cushing’s as well unless it’s psychological. Your WBCs are at a good number which would be lower with Cushings unless you are having an acute infection. Any UTI, ear infection, EENT infections, chest infection, poor wound healing, change in skin pigment? Definitely not anemic.

Is this new? What has changed most for you? Over how long do you think this has been developing (as far as you can figure)?

5

I do have a lot of ear infections. No on UTI. Not really sure what the gold standard would be on wound healing. Only change in skin pigment I can think of worth mentioning for the most part is that I have pretty dark circles under my eyes that don’t seem to improve based upon amount of sleep I’m getting.

Why would you say Cushing’s would suppress appetite when it is a cause of morbid obesity?

No, this isn’t new. Just in terms of hypogonadism, I didn’t really develop along the same lines as my brothers. One of them played football for Tennessee back when they weren’t terrible and was a first year started. I’m shorter, feel like I have underdeveloped genetalia. So wether it is Cushing’s or not, I think that this goes back to my childhood, and I’ve been fat since then as well.

6

The excess weight gain is due to ultra low metabolism and water retention. From the clients I’ve worked with that had cushings they had little interest in food. But since they can’t burn it with exercise and the metabolism never gets high enough to burn it they continue to gain until they start dying. Cushing’s is also a condition that can be corrected if it isn’t an adrenal problem.

Ever had any chromosomal testing? Checks for pituitary/hypothalamus tumors?

7

[quote]C27 H40 O3 wrote:
Ever had any chromosomal testing? Checks for pituitary/hypothalamus tumors?[/quote]
Nope and nope.

8

Had appt today. Will be doing a 24 hour urine cortisol test. Endo’s orders is 2000iu hCG 2x week IM. Shrugged off that I said according to what I’d been reading there wasn’t any benefit to IM over SubQ. Asked for an AI but was refused. Next appt in 4 weeks where T and E2 levels will be retested. Based on those numbers maybe an AI would be prescribed, and also at that point perhaps HMG will be added.

Unsure whether to follow Dr’s orders or just go ahead and do 250iu SubQ EOD.

9

2 reasons. 1. 2mL (probably what 2000iu’s will measure after reconstituting) is the MAX and not really the best method to deliver that much at once. 2. The IM route is a much faster administration route ESPECIALLY in obese patients. 2000iu’s is a large amount and there must be a rationale for hitting you hard and fast with hCG.

10

Following Dr’s orders then. The Pregnyl came in a 10000iu vial with 10mL bac water, but was instructed to only use 5mL when reconstituting. So injected dose is 1mL/2000iu. That twice a week for four weeks then T/E test. When we add HMG that will be SubQ, though. Only rationale I was told was wanting to see T hit some level before adding the HMG.

11

Doubt there is a cortisol issue. Sounds like a depression issue though and food is used as a crutch in some manner. A lethargy/slight melancholic depression can be caused by hormonal issues but morbid depression is deeper. Deeper than even neurotransmitters however the abrupt alterations in these seem to produce improvement in people such as through antidepressants. Figure out why you are depressed (through talk therapy as well…)

Why do you just have FSH? What about LH? HCG works like LH does. How are you responding? If you are doing well then we know your testicles are working. With obesity you certainly will have more estrogen dominance so estrogen issues will occur with more testosterone. I would have preferred a SERM than just HCG…especially since at least they have some antagonistic properties in areas that you do NOT want estrogen’s effects (like the breast!)…

12

Well, 24 hour cortisol is being tested, so should have some info about that by next week. Endo didn’t test LH. Today was first HCG injection, so too early to comment on effects.

I’ve been in therapy for over a year and also taking meds prescribed by my Pdoc. I’d say the meds raise the floor of my mood, but I’m far from feeling right.

As for breasts… well, actually the reason I was referred to this endo was for cross-sex HRT due to long standing gender issues uncovered in aforementioned talk therapy. At this point, I feel like the hypogonadism itself could potentially explain those gender issues, or at least it gives me a lot more doubt about transitioning. I’ve not wavered from wanting to preserve fertility before doing such a thing, and at this point I want to see what correct male hormonal ratio feels like before reconsidering that path. Hence MTFTM.

13

One interesting consideration is that insulin resistance has been linked to decreased leydig cell testosterone secretion. Another interesting researched item is that high levels of hCG can, in some cases, cause permanent growth and maturation of the leydig cells. This may be the rationale your Dr. is subscribing to.

14

As much as I’d love to quit my job and dive headfirst into researching Male Obesity-associated Secondary Hypogonadism (MOSH) as yet I have a tremendous amount to learn and hope to not fall victim to too many false assumptions as I learn. So let me just ask some of the questions I’m trying to find answers to in the research I am pursuing at this point.

Isn’t 60ng/dL too absurdly low to just suggest it is caused by aromatase from the obesity, even adding in that leydig cells may reduce secretion in insulin resistance? Maybe I’m underestimating my body’s ability to turn T into E, but that would just make it more frustrating to me that I wasn’t given an AI.

Also, while I’m sure my insulin sensitivity isn’t perfect by any stretch, I am not diabetic, and don’t even really feel like I have a lot of insulin resistance. When I learned about non-alcoholic fatty liver (years ago earlier in my journey in understanding my body and why I got fat), I spent a good amount of time supplementing choline and with zero fructose or alcohol in my diet. I haven’t had that experience of wanting to fall asleep after eating a large glucose load since then.

Not that my endo would know any of that since it hasn’t come up.

I also just find myself thinking since I’ve discovered that I have hypogonadism that it may be more a cause of than result of my obesity. So I want to think there is some underlying disruption of the HPT axis causing both, and at the moment Cushing’s really jumped out as a possibility to my lay knowledge.

Endo is sceptical but ordered the cortisol screen. Showed up at LabCorp with 24 hours of urine to be told that I had been given the wrong container and I’ll have to try again. So now that will be turned in Monday.

15

We are all learning here. I hope I can help but please second guess what I say and see if it is true for YOU.

The ability of excess fat to excrete aromatase enzymes is quite significant. This turns any free T it encounters into E2. E2 inhibits testosterone by negative feedback at the hypothalamus and stops LH and FSH from stimulating your testes. I think that with 30lbs extra body fat, a large portion of testosterone will be converted. Hence an extra 200lbs I would expect could obliterate it.

But I’m sure there’s more details to the story.

You mentioned fatty liver. Good start to illustrate how deep these matters run. The fatty liver cells are basically stressed out, tired and mechanically depleted hepatocytes that cannot contribute to your body function any more. These little guys are responsible for making almost every plasma protein in your body from clotting factors, albumin, and many other proteins like sex hormone binding globulin. These proteins transport testosterone and various other things around your body. In much the same way that hemoglobin transports oxygen to your tissues.

When CO2 levels are high (at oxygen depleted cells) the acidity causes the protein to change shape a little and the O2 pops off just in time to replenish the cell. When your free T is low the molecules of loosely bound T to albumin pop off in a similar fashion. The ones firmly attached to SHBG slowly dissociate and are then attached to albumin to replace the missing ones.

Ok, the free T can then act on androgen receptors BUT they also go back up to the hypothalamus and say I’m here we don’t need more (more negative feedback). So why did I explain all that you’re wondering? It’s because if there aren’t enough of these little protein factors floating around due to fatty liver, then more T will be free to inhibit production (don’t bother with the Free-T test it isn’t accurate).

Something else to consider; the ability of these messaging molecules (steroids derived from the same backbone that makes up cholesterol, testosterone, estrogen, progesterone etc.) to pass through the cell membranes is incredibly high! Unlike sodium and sugar they just drift into the nearest cell! You’re a substantial guy with some particularly large adipose cells where a boatload of steroids can hide and metabolize or be metabolically unavailable.

It must be very difficult to have to hear all the excess weight messages that are impossible to avoid but it’s so very important. Who cares about how it’s making you look. It’s messing with every function of your body. Beneath that extra weight there is probably DNA that could get your systems back and working like a while oiled machine and ready to kick some ass!

16

Oh, and in response to your hypothesis that the obesity induced hypogonadism may be a factor in sexual ambiguity: I would say almost absolutely. I don’t think we know enough about how testosterone creates sexuality or how environment affects it’s development to even begin to explain how this could be.

17

[quote]C27 H40 O3 wrote:
We are all learning here. I hope I can help but please second guess what I say and see if it is true for YOU.
[/quote]
I greatly appreciate you taking an interest in my case. Thanks!

[quote]C27 H40 O3 wrote:
The ability of excess fat to excrete aromatase enzymes is quite significant…Hence an extra 200lbs I would expect could obliterate it.
[/quote]
All the more reason that HCG without an AI should be considered to not help my T levels if it is just going to create more T to be aromatised into E.

[quote]C27 H40 O3 wrote:
It must be very difficult to have to hear all the excess weight messages that are impossible to avoid but it’s so very important. Who cares about how it’s making you look. It’s messing with every function of your body. Beneath that extra weight there is probably DNA that could get your systems back and working like a while oiled machine and ready to kick some ass![/quote]
It has been five years since I really seriously started trying to unravel my health and learn why I got fat. I really enjoy the puzzled look I got from my PCP when she good my blood work back and found I didn’t have diabetes or high cholesterol or high blood pressure while being over 400 pounds. It isn’t an accident.

I know that in many ways obesity is a comorbid symptom and not a cause of many of those diseases, and that cleaning up the diet can restore health in those areas more quickly and surely than it causes weight loss. I’m certain I’m not going to follow my father, aunt, brother into T2DM.

That doesn’t mean I understand all of the myriad causes that go into causing disordered eating in the first place. Learning about insulin and leptin resistance was very eye opening. In general I’m finding endocrinology fascinating. Or biochemistry generally. I bore friends regularly talking about things like fat soluble vitamins.

But for all I do know, I haven’t in practice succeeded at sustainable weight loss. None of the short term successes were sustainable. Last concerted effort from a high of 455 got down to 330 and it that was probably the third time in my life I’ve lost 75+ pounds. I know that yo-yo dieting is terrible, but I’m not going to give up trying to lose. But I haven’t really discovered why I eventually always hit a brick wall. Why it just keeps getting harder and harder until it finally is impossible. Why when I was at 330 and eating maintenance calories I felt like I was eating at a severe deficit. That isn’t sustainable. And here I am above 400 again.

So I’m still trying to really learn and understand why it’s just so hard. I’m driven. I have no shortage of will. But most of the time I have just felt like I was trying to brute force fight my own biochemistry. I’m still hoping as I learn more and make more changes I can make it easier. That eating a caloric deficit won’t feel like a starvation that will inevitably lead to a binge. That I will feel like I have some energy to spare to get under the bar and do some squats instead of just feeling like expending as little energy as possible and then sleep for twelve hours.

18

Well, the most important step towards health you’ve already taken and that is: you have taken responsibility for learning all you can about your health conditions and changing things to improve it’s management. If I could have every patient doing that I wouldn’t have a job.

In the case of obesity, sadly, it’s kind of a vicious cycle. The excess weight impedes weight loss and leeches away energy required to get it burning. The more I learn about biochemistry and fat loss, the more I believe it requires a certain endocrine environment to mobilize fat storage.

If I were to say begin a cardio regimen of 1hr every day right now I would lose all my muscle first before I ever saw my abs like some people have. I take 1/2mg of anastrozole and I can’t eat enough to maintain my weight to save my life. I’ve lost 12lbs this month and eating pizza and ice cream.

There’s more to it than all the diet crazes ever consider. Nutrient timing is a critical component to many endocrine functions. It would be cool to have a blood glucose monitor connected 24/7 with a wrist watch displaying the result in real time.

19

Finally got the result back for 24 hour cortisol test: 52ug, range 0-50.

Endo calls that normal.

20

1 Month on HCG test results:
T 221 range 348-1197 (up from 60)
E2 76.6 range 7.6-42 (up from 42)

Since E2 went up (of course it did) Endo has added a script for 2.5mg letrozole per day.

I’m just now starting to look at literature but isn’t 2.5mg a day WAY WAY too much? Most cases I’m seeing at a brief glance for hypogonadism secondary to obesity is saying 2.5mg a WEEK.